Evidence map›Paper›PMID 39607038›Full record

ArticlemAbs

Coactivation of Tie2 and Wnt signaling using an antibody-R-spondin fusion potentiates therapeutic angiogenesis and vessel stabilization in hindlimb ischemia.

Byungtae Hwang, Min-Young Jeon, Ju-Hong Jang, Young-Lai Cho, Dong Gwang Lee, Jeong-Ki Min, Jangwook Lee, Jong-Gil Park, Ji-Hun Noh, Wonjun Yang and 1 more

Abstract read
In one paragraph

Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Byungtae HwangBiotherapeutics Translational Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon, Republic of Korea.
Min-Young JeonBiotherapeutics Translational Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon, Republic of Korea.
Ju-Hong JangBiotherapeutics Translational Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon, Republic of Korea.
Young-Lai ChoEnvironmental Diseases Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea.
Dong Gwang LeeBiotherapeutics Translational Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon, Republic of Korea.
Jeong-Ki MinBiotherapeutics Translational Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon, Republic of Korea.
Jangwook LeeBiotherapeutics Translational Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon, Republic of Korea.
Jong-Gil ParkBiotherapeutics Translational Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon, Republic of Korea.
Ji-Hun NohDepartment of Biochemistry, College of Natural Sciences, Chungnam National University, Daejeon, Republic of Korea.
Wonjun YangBiotherapeutics Translational Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon, Republic of Korea.
Nam-Kyung LeeBiotherapeutics Translational Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon, Republic of Korea.

Funding

Korea Research Institute of Bioscience and Biotechnology (KRIBB) Research Initiative Program KGM5272324the Ministry of Education NRF-2021R1I1A2057698
6 · The paper itself

Abstract

Therapeutic angiogenesis by intentional formation of blood vessels is essential for treating various ischemic diseases, including limb ischemia. Because Wnt/β-catenin and angiopoietin-1/Tie2 signaling play important roles in endothelial survival and vascular stability, coactivation of these signaling pathways can potentially achieve therapeutic angiogenesis. In this study, we developed a bifunctional antibody fusion, consisting of a Tie2-agonistic antibody and the Furin domains of R-spondin 3 (RSPO3), to simultaneously activate Tie2 and Wnt/β-catenin signaling. We identified a Tie2-agonistic antibody T11 that cross-reacted with the extracellular domain of human and mouse Tie2, and evaluated its ability to increase endothelial cell survival and tube formation. We generated a bifunctional T11-RF12 by fusing T11 with the Furin-1 and -2 domains of RSPO3. T11-RF12 could bind not only to Tie2, but also to LGR5 and ZNRF3, which are counterparts of the Furin-1 and -2 domains. T11-RF12 significantly increased Wnt/β-catenin signaling, as well as the formation of capillary-like endothelial tubes, regardless of the presence of Wnt ligands. Coactivation of Tie2 and Wnt/β-catenin signaling by T11-RF12 increased the blood flow, and thereby reduced foot necrosis in a mouse hindlimb ischemia model. In particular, T11-RF12 induced therapeutic angiogenesis by promoting vessel stabilization through pericyte coverage and retaining endothelial expression of Frizzled 10 and active β-catenin. These results indicate that the agonistic synergism of Tie2 and Wnt/β-catenin signaling achieved using T11-RF12 is a novel therapeutic option with potential for treating limb ischemia and other ischemic diseases.

Indexed as

HindlimbIschemiaNeovascularization, PhysiologicReceptor, TIE-2Recombinant Fusion ProteinsThrombospondinsWnt Signaling PathwayAngiogenesisAnimalsHumansHuman Umbilical Vein Endothelial CellsMiceReceptor, TIE-2Recombinant Fusion ProteinsTek protein, mouseThrombospondinsBifunctional antibodyhindlimb ischemiaR-spondintherapeutic angiogenesisTie2vessel stabilizationWnt

Identifiers

PMID39607038
PMCPMC11610559

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LicenceCC BY-NC
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.